Long-Term Precision of 18F-Fluoride PET Skeletal Kinetic Studies in the Assessment of Bone Metabolism

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Abstract
18F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed Ki, reflects regional bone metabolism. The aim of this study was to compare the long-term precision of 18F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. Methods: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent 18F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the 18F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (Ki-4k), a 3k 3-compartmental model using nonlinear regression analysis (Ki-3k), Patlak analysis (Ki-PAT), and standardized uptake values. Results: With the exception of a small but significant decrease in Ki-3k at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%–19%), 13.8% (10%–22%), 14.4% (11%–22%), and 26.6% (19%–40%) for Ki-3k, Ki-PAT, mean standardized uptake value, and Ki-4k, respectively. For comparison, the precision of the biochemical markers was 10% (7%–15%), 18% (13%–27%), and 14% (10%–21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for Ki-4k to 0.85 for Ki-3k. No significant correlation was found between the repeated mean standardized uptake value measurements. Conclusion: The precision and intraclass correlation observed for Ki-3k and Ki-PAT was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of 18F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.

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